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Fragile X—A Family of Disorders: Changing Phenotype and Molecular Genetics

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The Principles of Clinical Cytogenetics

Abstract

In 1938, Penrose noted a higher incidence of mental retardation (MR) in males and reports of families with only affected males (Penrose, A clinical and genetic study of 1,280 cases of mental defect. Special report series no. 229. Medical Research Council, London, 1938). These observations were compatible with X-linked inheritance, and numerous reports appeared in the literature (Howard-Peebles, J Ment Defic Res 26: 205–213, 1982). Based on this early work, a clinically nonspecific X-linked MR disorder was delineated and called Renpenning’s syndrome, Martin-Bell syndrome, or nonspecific X-linked MR. In 1959, Lubs described the first family with cytogenetic expression of the “marker X,” which became the fragile X (fraX), and the heterogeneity of this nonspecific X-linked MR disorder became apparent (Lubs, Am J Hum Genet 21: 231–244, 1969). Numerous disorders have been delineated from this original subgroup of MR males. The fraX subgroup was unique because there was a diagnostic laboratory test; the name Martin-Bell syndrome was attached when this family, first described in 1943, was shown to be positive for the fraX (Hamel et al, Am J Med Genet 94: 361–363, 2000), (Martin and Bell, J Neurol Psychiatry 6:154–157, 1943). However, the popular name for this disorder became fragile X syndrome (FXS).

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Acknowledgments

The author would like to thank Patricia N. Howard-Peebles, author of the chapter in previous editions, for providing the general scope and framework of the material.

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    Elaine B. Spector Ph.D.

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Spector, E.B. (2013). Fragile X—A Family of Disorders: Changing Phenotype and Molecular Genetics. In: Gersen, S., Keagle, M. (eds) The Principles of Clinical Cytogenetics. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1688-4_19

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